4.7 Article

EColiCore2: a reference network model of the central metabolism of Escherichia coli and relationships to its genome-scale parent model

期刊

SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/srep39647

关键词

-

资金

  1. German Federal Ministry of Education and Research [FKZ: 031A180B]

向作者/读者索取更多资源

Genome-scale metabolic modeling has become an invaluable tool to analyze properties and capabilities of metabolic networks and has been particularly successful for the model organism Escherichia coli. However, for several applications, smaller metabolic (core) models are needed. Using a recently introduced reduction algorithm and the latest E. coli genome-scale reconstruction iJO1366, we derived EColiCore2, a model of the central metabolism of E. coli. EColiCore2 is a subnetwork of iJO1366 and preserves predefined phenotypes including optimal growth on different substrates. The network comprises 486 metabolites and 499 reactions, is accessible for elementary-modes analysis and can, if required, be further compressed to a network with 82 reactions and 54 metabolites having an identical solution space as EColiCore2. A systematic comparison of EColiCore2 with its genome-scale parent model iJO1366 reveals that several key properties (flux ranges, reaction essentialities, production envelopes) of the central metabolism are preserved in EColiCore2 while it neglects redundancies along biosynthetic routes. We also compare calculated metabolic engineering strategies in both models and demonstrate, as a general result, how intervention strategies found in a core model allow the identification of valid strategies in a genome-scale model. Overall, EColiCore2 holds promise to become a reference model of E. coli's central metabolism.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Biochemical Research Methods

An extended and generalized framework for the calculation of metabolic intervention strategies based on minimal cut sets

Philipp Schneider, Axel von Kamp, Steffen Klamt

PLOS COMPUTATIONAL BIOLOGY (2020)

Article Biotechnology & Applied Microbiology

Increasing ATP turnover boosts productivity of 2,3-butanediol synthesis in Escherichia coli

Simon Boecker, Bjoern-Johannes Harder, Regina Kutscha, Stefan Pfluegl, Steffen Klamt

Summary: Enforced ATP wasting through overexpressing the genes of the ATP-hydrolyzing F-1-part of the ATPase significantly increased the yield and productivity of 2,3-BDO synthesis in E. coli. The ATPase strain outperformed the control strain in specific substrate uptake and 2,3-BDO synthesis rate, leading to the design of a three-stage process for optimal glucose to 2,3-BDO conversion with high productivity and yield.

MICROBIAL CELL FACTORIES (2021)

Article Biochemical Research Methods

Systematizing the different notions of growth-coupled product synthesis and a single framework for computing corresponding strain designs

Philipp Schneider, Radhakrishnan Mahadevan, Steffen Klamt

Summary: This paper proposes an ontology for different degrees of growth-coupled product synthesis and extends the Minimal Cut Sets (MCS) framework to allow computation of designs for all GCP classes within a single framework. The study illustrates hierarchical relationships between coupling degrees and shows that feasibility of coupling is not affected by the chosen GCP degree. The principle of coupling can be generalized to couple product synthesis with other cellular functions beyond growth.

BIOTECHNOLOGY JOURNAL (2021)

Article Biochemical Research Methods

Designing microbial communities to maximize the thermodynamic driving force for the production of chemicals

Pavlos Stephanos Bekiaris, Steffen Klamt

Summary: Microbial communities are crucial for biogeochemical cycles, biomedicine, and biotechnological applications. While naturally arising communities are used in some processes, the design of synthetic microbial consortia for bio-based production has gained interest. A new computational approach, ASTHERISC, has been developed to design single-species multi-strain communities for maximizing thermodynamic driving force for product synthesis. This approach shows potential for improving microbial community design for chemical production.

PLOS COMPUTATIONAL BIOLOGY (2021)

Article Engineering, Chemical

Maximizing batch fermentation efficiency by constrained model-based optimization and predictive control of adenosine triphosphate turnover

Sebastian Espinel-Rios, Katja Bettenbrock, Steffen Klamt, Rolf Findeisen

Summary: The paper presents a constrained model-based optimization and predictive control framework to maximize the production efficiency of batch fermentations by manipulating ATP wasting. By formulating ATP wasting as a model-based optimal control problem, the trade-offs between product yield and volumetric productivity can be balanced. The approach incorporates moving horizon model predictive control and constraint-based dynamic modeling to overcome model-plant mismatch, disturbances, and uncertainties.

AICHE JOURNAL (2022)

Article Biochemical Research Methods

CNApy: a CellNetAnalyzer GUI in Python for analyzing and designing metabolic networks

Sven Thiele, Axel von Kamp, Pavlos Stephanos Bekiaris, Philipp Schneider, Steffen Klamt

Summary: CNApy is an open-source desktop application written in Python that offers a graphical interface for analyzing metabolic networks. It supports various COBRA techniques and allows for easy extension of functionalities.

BIOINFORMATICS (2022)

Article Biochemistry & Molecular Biology

Deciphering the physiological response of Escherichia coli under high ATP demand

Simon Boecker, Giulia Slaviero, Thorben Schramm, Witold Szymanski, Ralf Steuer, Hannes Link, Steffen Klamt

Summary: This study systematically analyzed the impact of different ATP demands on glycolytic flux in Escherichia coli, revealing a biphasic behavior induced by the dual dependency of phosphofructokinase on ATP and ADP. The results provide insights into fundamental mechanisms of bacterial energy metabolism and offer guidance for the rational design of highly productive cell factories. Model analysis confirmed major rate-controlling steps in glycolysis under high ATP demand, which were experimentally validated.

MOLECULAR SYSTEMS BIOLOGY (2021)

Article Biotechnology & Applied Microbiology

Enabling anaerobic growth of Escherichia coli on glycerol in defined minimal medium using acetate as redox sink

Simon Boecker, Sebastian Espinel-Rios, Katja Bettenbrock, Steffen Klamt

Summary: A novel strategy for fermentative growth of Escherichia coli on glycerol in defined minimal medium was proposed and validated through model-based calculations. The strategy involved the uptake of small amounts of acetate with subsequent reduction to ethanol, which enabled redox balance in the anaerobic conditions. The study also generated an E. coli strain that exhibited robust growth, high glycerol uptake rate, and near-maximum ethanol yield, offering new perspectives for sustainable production processes based on glycerol.

METABOLIC ENGINEERING (2022)

Article Biochemistry & Molecular Biology

Analyzing and Resolving Infeasibility in Flux Balance Analysis of Metabolic Networks

Steffen Klamt, Axel von Kamp

Summary: Flux balance analysis (FBA) is a crucial method for analyzing metabolic networks, but it may encounter infeasible scenarios. This article presents and compares two methods, based on linear programming (LP) and quadratic programming (QP), to address the infeasibility of FBA problems. The authors provide practical guidance on handling infeasible FBA systems and discuss relevant examples. Additionally, they highlight the relationships to classical metabolic flux analysis.

METABOLITES (2022)

Article Biochemical Research Methods

StrainDesign: a comprehensive Python package for computational design of metabolic networks

Philipp Schneider, Pavlos Stephanos Bekiaris, Axel von Kamp, Steffen Klamt

Summary: This article introduces a Python package called StrainDesign, which is built upon the COBRApy toolbox and integrates various metabolic design algorithms. The package provides advanced features and enhanced tools for analyzing computed intervention strategies.

BIOINFORMATICS (2022)

Article Biochemical Research Methods

Zymo-Parts: A Golden Gate Modular Cloning Toolbox for Heterologous Gene Expression in Zymomonas mobilis

Gerrich Behrendt, Jonas Frohwitter, Maria Vlachonikolou, Steffen Klamt, Katja Bettenbrock

Summary: Zymo-Parts is a modular toolbox based on Golden-Gate cloning that enables efficient construction of genetically modified strains. It offers a collection of promoters, terminators, ribosomal binding sites, and reporter genes for achieving desired levels of gene expression. The GoldenBraid-based system allows for the assembly of operons with multiple genes. The utility of Zymo-Parts for metabolic engineering applications is demonstrated by overexpressing a heterologous lactate dehydrogenase gene in Z. mobilis.

ACS SYNTHETIC BIOLOGY (2022)

Article Biotechnology & Applied Microbiology

Characterizing and utilizing oxygen-dependent promoters for efficient dynamic metabolic engineering

Julian Wichmann, Gerrich Behrendt, Simon Boecker, Steffen Klamt

Summary: This study systematically tested and characterized 15 promoter candidates that are induced upon oxygen depletion in Escherichia coli. Six of these promoters are particularly suited for dynamic metabolic engineering applications. The study also demonstrated the optimization of a two-stage lactate production process using these promoters.

METABOLIC ENGINEERING (2023)

Article Multidisciplinary Sciences

Network-wide thermodynamic constraints shape NAD(P)H cofactor specificity of biochemical reactions

Pavlos Stephanos Bekiaris, Steffen Klamt

Summary: The study presents a computational framework to analyze the impact of redox cofactor swaps on the thermodynamic potential of a metabolic network. It suggests that the specificity of NAD(P)H reactions is influenced by the metabolic network structure, enabling thermodynamic driving forces close to the theoretical optimum.

NATURE COMMUNICATIONS (2023)

Article Biotechnology & Applied Microbiology

Toward a modeling, optimization, and predictive control framework for fed-batch metabolic cybergenetics

Sebastian Espinel-Rios, Bruno Morabito, Johannes Pohlodek, Katja Bettenbrock, Steffen Klamt, Rolf Findeisen

Summary: Biotechnology provides opportunities for sustainable production of valuable products. Optimization tools include both extracellular process elements and intracellular metabolic and genetic engineering methods. The concept of cybergenetics coupled with model-based optimization and predictive control enables online modulation of gene expression and feedback control to achieve optimal performance in dynamic bioprocesses. Fed-batch processes and substrate feeding rate optimization are used as examples to demonstrate the application of these methods.

BIOTECHNOLOGY AND BIOENGINEERING (2023)

Article Biochemical Research Methods

Balancing biomass reaction stoichiometry and measured fluxes in flux balance analysis

Axel von Kamp, Steffen Klamt

Summary: In this study, a method is presented to modify the stoichiometry of the biomass reaction in order to make the flux balance analysis problem feasible and improve the accuracy of the model. Realistic flux measurements of E.coli are used to demonstrate the value of this approach, highlighting the overestimation of growth-associated maintenance (GAM) demand of ATP in recent genome-scale models.

BIOINFORMATICS (2023)

暂无数据